This is a renewal application to RFA-HL-17-018 to propose that Division of Blood and Marrow Transplantation (BMT) at Stanford University continue as a Core Clinical Center for the BMT Clinical Trials Network (BMT CTN). Stanford's Program will perform about 380 adult transplants in 2016 including autologous and allogeneic transplants using cells from matched and mismatched related and unrelated donors, cord blood units, ex vivo manipulated cell products and genetically modified cells. Stanford's BMT Program participates in basic, and clinical research as a single institution, and within regional, national and international consortia. The division is supported by a National Institutes of Health (NIH) Program Project Grant with over 27 years of funding of basic scientific research, and clinical translational trials that advance the field. The Program is strengthened by highly experienced biostatics and data management groups, and a cGMP-compliant, FACT and CLIA certified Cellular Therapy Facility for routine cell processing and the development of investigational cellular therapies. The Program is a high accrual BMT CTN center and has enrolled 320 patients to 16 CTN studies. In the past granting period, Stanford investigators served as Chair of the BMT CTN Steering Committee, Chair to the Lymphoma Symposium Committee, and have been members on five CTN committees and one Task Force. Stanford will continue to leverage the capabilities of its Program to support the research goals of the CTN. It is our collective mission to advance the field of BMT for patients with rare and difficult to treat blood diseases through high quality multi-center clinical trials. The goal of the proposed protocol in the current application is to determine if a novel strategy can reduce the risk of developing chronic GVHD (cGVHD) and thereby improve upon traditional allogeneic BMT. We propose a randomized phase 3 clinical trial where the active comparator is Ibrutinib starting 90 days after transplant and the control arm is no additional cGVHD prevention strategy. This study builds upon our prior preclinical and clinical work with this agent for the treatment and prevention of cGVHD. The primary outcome measure will be the rate of steroid requiring cGVHD by 18 months after transplant. Based on an aggregate of data, we hypothesize that Ibrutinib will reduce cGVHD development due to its ability to block B cell activation via irreversible inhibition of Bruton's tyrosine kinase (BTK) and its ability to block T helper subset activation from inhibition of IL-2 inducible T cell kinase (ITK). The Stanford BMT program is committed to continued participation in BMT CTN trials, contributing concepts for consideration by the Network, and participating in Network committees and citizenship activities. !